Cook C D, Barrett A C, Roach E L, Bowman J R, Picker M J
Department of Psychology, University of North Carolina at Chapel Hill, 27599-3270, USA.
Psychopharmacology (Berl). 2000 Jul;150(4):430-42. doi: 10.1007/s002130000453.
Recent studies indicate that morphine is more potent as an antinociceptive agent in male than female rodents and monkeys.
To evaluate the influence of sex, nociceptive stimulus intensity and an opioid's relative efficacy on opioid-induced antinociception in rat strains (F344 and Lewis) that display differential sensitivity to morphine antinociception.
Antinociceptive testing was conducted using a rat warm-water (50-56 degrees C) tail-withdrawal procedure. Dose-response and time-course determinations were performed with various opioids.
Across the nociceptive stimulus intensities tested, the high-efficacy mu opioids morphine, etorphine, and levorphanol were equally effective in males and females, but on average 2.5-fold more potent in males. At moderate stimulus intensities, the low-efficacy mu opioid buprenorphine was approximately 0.4-fold more potent in males, and at higher stimulus intensities more potent and effective (greater maximal effect) in males. At low stimulus intensities, the low-efficacy mu opioid dezocine and the mu/kappa opioid butorphanol were greater than 8.9-fold more potent in males, and at moderate stimulus intensities were more potent and effective in males. At a low stimulus intensity, the mu/kappa opioid nalbuphine was more potent and effective in males. At stimulus intensities in which buprenorphine, dezocine, butorphanol, and nalbuphine produced maximal effects in males but not females, these opioids antagonized the effects of morphine in females. Genotype-related differences were noted as opioids were generally more potent in F344 than Lewis males, whereas no consistent differences were observed between F344 and Lewis females.
That sex differences in the potency and effectiveness of opioids increased with decreases in the opioid's relative efficacy and with increases in the nociceptive stimulus intensity suggests that the relative efficacy of mu opioids as antinociceptive agents is greater in male than female rats.
最近的研究表明，在雄性啮齿动物和猴子中，吗啡作为一种抗伤害感受剂比雌性更有效。
评估性别、伤害性刺激强度和阿片类药物的相对效力对显示出对吗啡抗伤害感受有不同敏感性的大鼠品系（F344和Lewis）中阿片类药物诱导的抗伤害感受的影响。
使用大鼠温水（50 - 56摄氏度）甩尾程序进行抗伤害感受测试。用各种阿片类药物进行剂量反应和时间过程测定。
在所测试的伤害性刺激强度范围内，高效能μ阿片类药物吗啡、埃托啡和左啡诺在雄性和雌性中同样有效，但在雄性中的效力平均高2.5倍。在中等刺激强度下，低效能μ阿片类药物丁丙诺啡在雄性中的效力约高0.4倍，在较高刺激强度下在雄性中效力更高且效果更好（最大效应更大）。在低刺激强度下，低效能μ阿片类药物地佐辛和μ/κ阿片类药物布托啡诺在雄性中的效力大于8.9倍更高，在中等刺激强度下在雄性中效力更高且效果更好。在低刺激强度下，μ/κ阿片类药物纳布啡在雄性中效力更高且效果更好。在丁丙诺啡、地佐辛、布托啡诺和纳布啡在雄性而非雌性中产生最大效应的刺激强度下，这些阿片类药物拮抗了吗啡在雌性中的作用。注意到基因型相关差异，因为阿片类药物在F344雄性中通常比Lewis雄性更有效，而在F344和Lewis雌性之间未观察到一致差异。
阿片类药物效力和效果的性别差异随着阿片类药物相对效力的降低和伤害性刺激强度的增加而增加，这表明μ阿片类药物作为抗伤害感受剂在雄性大鼠中的相对效力大于雌性大鼠。
